Automated Macrodissection Device

描述(申请人提供)：固定在玻璃片上的福尔马林固定石蜡包埋(FFPE)组织切片的显微镜检查是临床组织病理学的基石。辅助分子检测通常是诊断、风险分层和治疗计划所必需的，尤其是在癌症中。分子检测通常涉及从FFPE组织切片中提取的核酸(DNA和RNA)的突变或表达分析。由于组织的异质性，通常使用现有的解剖方法从FFPE组织切片的解剖区域中分离出核酸，包括：手动宏观解剖、手动显微解剖和激光捕获显微解剖(LCM)。这一阶段的拨款申请是为临床医生开发一种自动化宏观解剖设备，该设备显著提高了生产率和结果质量，领先于现有的竞争设备和方法。拟议的第一阶段项目的目标是开发一种新型系统，该系统包括一个软件应用程序和用户界面，使病理学家能够在组织切片的数字图像上指示病变的区域。该软件将把感兴趣的区域转移到新的全自动12载玻片组织切除和修复仪器上的二级载玻片上。新仪器将是一个计算机控制系统，将包括x.y.z定位，集成光学系统，以及多种专门的组织移除和修复提示选择。使用图像识别，系统将自动识别感兴趣的组织切片区域 二次载玻片，将专门的尖端移过该区域，将组织碎片从载玻片表面移位，同时回收含有悬浮组织切片碎片的液体，用于辅助分子测试。该系统将基于解剖技术公司发明，并获得犹他大学ARUP实验室的独家许可。随后的商用仪器将满足临床市场对高通量宏观解剖(分辨率低至0.25 mm)仪器的需求，该仪器具有完全自动化、过程监控和报告、易于使用、具有手动解剖技术的恢复效率，但具有更高的精度。该系统将在组织图像识别能力、幻灯片到幻灯片的缩放和配准以及与初级数字病理成像系统的集成能力方面进行验证。该系统还将验证机械自动化性能，包括12张幻灯片的载玻片基准和自动X.Y？校正协议，以及自动消耗品装载和样品处理。最终，该系统还将在解剖分辨率、组织恢复的效率和准确性方面进行验证。基于数字成像系统的模型系统、12个载玻片批次以及定义的组织类型和载玻片类型集合来定义验证策略。通过量化第一阶段在原型仪器上的成像、机械和解剖性能，我们将论证第二阶段开发和商业化的可行性。 与公共健康相关：自动化宏观解剖设备将提供一个价格非常实惠的自动化系统，用于集成数字载玻片成像以及每批最多12个载玻片的可拆卸组织解剖和恢复。集成成像将加快病理学家对需要进行显微解剖的切片的审查，并将通过数字病理学与专家病理学家进行会诊。该系统将改进流程文件和核查，加强电子病历的努力。该设备的技术性能包括解剖分辨率低至0.25毫米，投资比激光捕获微解剖技术低一个数量级，使人们能够更广泛地接触到这项新技术。这一新设备将提高癌症诊断以及癌症和非癌症研究领域的临床医生的工作效率和结果质量，这些领域需要从载玻片上进行高通量组织解剖。

DESCRIPTION (provided by applicant): Microscopic examination of formalin fixed, paraffin embedded (FFPE) tissue sections mounted on glass slides is the cornerstone of clinical histopathology. Ancillary molecular testing is often required for diagnosis, risk stratification, ad treatment planning, particularly in cancer. Molecular testing often involves mutation or expression analysis of nucleic acids (DNA and RNA) recovered from FFPE tissue sections. Due to tissue heterogeneity, nucleic acids are often isolated from dissected regions of the FFPE tissue section using current dissection methods, including: Manual Macrodissection, Manual Microdissection, and Laser Capture Microdissection (LCM). This Phase I grant application is for the development of an Automated Macrodissection Device for clinicians that significantly advances productivity and quality of results ahead of existing competitive devices and methods. The goal of the proposed Phase I project is to develop a novel system that encompasses a software application and user interface that will allow a pathologist to indicate an area of interet on a digital image of a tissue section. The software will transfer that area of interest to secondary slides on a new fully automated 12 slide tissue removal and recovery instrument. The new instrument will be a computer controlled system that will includes x.y.z positioning, integrated optics, and multiple choices of specialized tissue removal and recovery tips. Using image recognition the system will automatically identify the tissue section area of interest on the secondary slide, move the specialized tip over this area to displace tissue fragments from the slide surface, and simultaneously recover the liquid containing the suspended tissue section fragments for the ancillary molecular testing. The system will be based on dissection technology co.invented and exclusively licensed from the University of Utah's ARUP Laboratories. The subsequent commercial instrument would fill the need in the clinical market for a high throughput macrodissection (down to 0.25mm resolution) instrument with full automation, process monitoring and reporting, ease of use, with the recovery efficiency of manual dissection techniques, but with far better precision. The system will be validated for tissue image recognition capability, slide to slide scaling and registration, and the capability for integrationto primary digital pathology imaging systems. The system will also be validated for mechanical automation performance including both slide fiducial and automated x.y.¿ correction protocols for 12 slides as well as automated consumable loading and sample handling. Ultimately, the system will also be validated for dissection resolution, efficiency, and accuracy of tissue recovery. Validation strategies are defined based on a model system of digitally imaging system, 12 slide batches, and a defined set of tissue types and slide types. By quantifying the imaging, mechanical and dissection performance in Phase I on prototype instruments, we will demonstrate feasibility for Phase II development and commercialization. PUBLIC HEALTH RELEVANCE: The Automated Macrodissection Device will provide a highly affordable automated system for integrated digital slide imaging and walk-away tissue dissection and recovery for up to twelve slides per batch. The integrated imaging will expedite pathologist review of slides requiring microdissection and will enable consultation with expert pathologists via digital pathology. The system will improve process documentation and verification, enhancing the efforts toward electronic medical records. The device's technical performance includes a dissection resolution down to 0.25mm and an order of magnitude lower investment than that required for laser capture microdissection technologies, enabling much broader access to the new technology. The new device will promote productivity and quality of results for clinicians working in cancer diagnostics, as well as diverse areas of cancer and non-cancer research requiring high throughput tissue dissection from slides.